Evolutionary scenarios for the specific recognition of nonhomologous endogenous peptides by G protein-coupled receptor paralogs.

ABSTRACT: Several peptides interact with phylogenetically unrelated G protein-coupled receptors (GPCRs); similarly, orthologous GPCRs interact with distinct ligands. The neuropeptide substance P (SP) activates both NK1R and another unrelated primate-specific GPCR, MRGPRX2. Furthermore, MRGPRX1, a paralog of MRGPRX2, recognizes BAM8-22 (bovine adrenal medulla peptide 8-22), which has no evolutionary relatedness to SP. To elucidate the molecular basis and evolutionary history of this phylogenetically unrelated ligand selectivity, we developed a systematic procedure, the "interaction determinant likelihood score" system, which estimates the amino acid residues responsible for peptide-GPCR interactions predicted by peptide descriptor-incorporated support vector machine, our original machine learning-bas

SUBMITTER: Shiraishi A 

PROVIDER: S-EPMC11910321 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature